This research project will focus on establishing the mechanisms of induction of and action of macrophages (M phi) in their antiviral and antitumor functions. It has long been recognized that M phi play a major role in the host response to viral infections, and in the last few years it has become apparent that M phi are a major effector of resistance to tumor growth. M phi are required for induction of many specific humoral and cell mediated immune responses, as well as serving an amplifying effector function that may either be protective or immunopathogenic. Moreover, M phi appear to exert a broad nonimmunospecific regulatory role in proliferative events. Thus immunologic/pharmacologic intervention at the level of the M phi has enormous possibilities for controlling viral, neoplastic, and auto-immune disease processes. Before these goals can be realized, we need to define the interactions of M phi with specific immunologic and nonspecific processes, and the mechanisms of M phi action. The overall objectives of this research project are to: (1) establish the mechanisms of induction of M phi mediated extrinsic antiviral activity; (2) establish the mechanisms of action of M phi mediated extrinsic antiviral activity; and (3) define the relationships among the antiviral, antitumor and biochemical functions of M phi. To achieve these goals the experimental approaches will include use of the lysosomally deficient M phi of the C57B1/6N beige mouse, and the cell separation capability of the FACS cell sorter. The goal of these studies is to determine the common and unique bases for M phi biologic functions, and to determine whether separate M phi functional subclasses exist or whether M phi can be modulated from one function to another.